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Review
. 2024 Apr:125:102703.
doi: 10.1016/j.ctrv.2024.102703. Epub 2024 Mar 4.

Tumor-agnostic baskets to N-of-1 platform trials and real-world data: Transforming precision oncology clinical trial design

Affiliations
Review

Tumor-agnostic baskets to N-of-1 platform trials and real-world data: Transforming precision oncology clinical trial design

Elena Fountzilas et al. Cancer Treat Rev. 2024 Apr.

Abstract

Choosing the right drug(s) for the right patient via advanced genomic sequencing and multi-omic interrogation is the sine qua non of precision cancer medicine. Traditional cancer clinical trial designs follow well-defined protocols to evaluate the efficacy of new therapies in patient groups, usually identified by their histology/tissue of origin of their malignancy. In contrast, precision medicine seeks to optimize benefit in individual patients, i.e., to define who benefits rather than determine whether the overall group benefits. Since cancer is a disease driven by molecular alterations, innovative trial designs, including biomarker-defined tumor-agnostic basket trials, are driving ground-breaking regulatory approvals and deployment of gene- and immune-targeted drugs. Molecular interrogation further reveals the disruptive reality that advanced cancers are extraordinarily complex and individually distinct. Therefore, optimized treatment often requires drug combinations and N-of-1 customization, addressed by a new generation of N-of-1 trials. Real-world data and structured master registry trials are also providing massive datasets that are further fueling a transformation in oncology. Finally, machine learning is facilitating rapid discovery, and it is plausible that high-throughput computing, in silico modeling, and 3-dimensional printing may be exploitable in the near future to discover and design customized drugs in real time.

Keywords: Biomarkers; Clinical trial design; Master protocol; N-of-1; Precision oncology; Real world data.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Elena Fountzilas has the following financial relationships to disclose: Advisory Role: Amgen. Speaker fees: Pfizer, AstraZeneca, Amgen, GSK. Travel grant: AstraZeneca, Pfizer and Genesis. Stock ownership: Genprex Inc., Deciphera Pharmaceuticals Inc. Dr. Apostolia-Maria Tsimberidou has the following financial relationships to disclose: Clinical Trial Research Funding (Institution): OBI Pharma, Agenus, Parker Institute for Cancer Immunotherapy, Tempus, IMMATICS, Tvardi, Novocure, Tachyon, Orionis; Consulting or Advisory Role: VinceRx, Diaccurate, NEX-I; BrYet, Bioeclipse, Macrogenics, Avstera Therapeutics. Other: Travel: ASCO, Cancer Care Crossroads, Precision Medicine World Conference, GenomeWeb conference. Dr. Henry Hiep Vo reports no relevant conflicts of interest. Dr. Kurzrock has received research funding from Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte,Konica Minolta, Medimmune, Merck Serono, Omniseq, Pfizer, Sequenom, Takeda, and TopAlliance and from the NCI;as well as consultant and/or speaker fees and/or advisory board/consultant for Actuate Therapeutics, AstraZeneca, Bicara Therapeutics, Inc., Biological Dynamics, Caris, Datar Cancer Genetics, Daiichi, EISAI, EOM Pharmaceuticals, Iylon, LabCorp, Merck, NeoGenomics, Neomed, Pfizer, Prosperdtx, Regeneron, Roche, TD2/Volastra, Turning Point Therapeutics, X-Biotech; has an equity interest in CureMatch Inc. and IDbyDNA; serves on the Board of CureMatch and CureMetrix, and is a co-founder of CureMatch. RK is funded in part by 5U01CA180888-08 and 5UG1CA233198-05.

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